Effects of long-term combined dosing with nicardipine and propranolol on coronary hemodynamics, myocardial metabolism, and exercise tolerance in patients with angina pectoris: comparison with monotherapy.

To determine whether the association of nicardipine with propranolol had additive effects on myocardial metabolism, 16 patients with angina pectoris were studied invasively before and after 1 month of therapy with a combination of nicardipine and propranolol and compared to a group of 42 patients treated with nicardipine (n = 17) or propranolol (n = 25) alone. When data were compared at a fixed heart rate (atrial pacing), mean blood pressure was reduced with combined treatment from 96 +/- 19 to 76 +/- 13 mm Hg (p less than 0.003). Myocardial oxygen uptake and coronary sinus flow decreased significantly from 20 +/- 9 to 14 +/- 6 ml/min (p less than 0.015) and from 152 to 111 ml/min (p less than 0.05), respectively. The arterio-coronary sinus difference in oxygen content also decreased (13.3 to 12.5 ml/dl; p less than 0.0025), suggesting an improved balance between oxygen supply and demand. Such changes in coronary blood flow and myocardial oxygen uptake were not observed in the group of patients assigned to monotherapy. Lactate uptake rose and the abnormal glutamine production, which worsened with propranolol monotherapy, improved with nicardipine and propranolol (-2.0 to -1.4 mumol/min; p less than 0.05 vs propranolol). The superiority of nicardipine and propranolol over propranolol monotherapy was maintained during a pacing stress test. Thus the combination of nicardipine with a beta blocker had greater oxygen-sparing effects and restored aerobic metabolism better than either drug alone, allowing optimal use of the coronary reserve.

Antiallergic effects of the new histamine H1-receptor antagonist tazifylline in healthy atopic and non-atopic subjects.

Single oral doses (5, 10 and 15 mg) of the new H1-receptor antagonist 3,7-dihydro-7-[2-hydroxy-3-[4-[3-phenylthio) propyl]-1-piperazinyl]propyl-1,3-dimethyl-1H-purine-2,6-dione dihydrochloride (tazifylline, RS-49014) were administered at 7-day intervals to 12 atopic and 12 non-atopic volunteers in a double-blind randomised cross-over study. Antiallergic activity was evaluated from pre to 60 min post dose inhibitions of wheal and flare areas provoked by various cutaneous challenges. Atopic subjects showed greater skin reactivity than non-atopics to some challenges. Tazifylline was associated (in atopics and non-atopics) with statistically significant dose related inhibitions, of flare over 5-15 mg and of wheal (10-15 mg) induced by the more potent and reproducible challenges of codeine, 1% histamine and anti-IgE. Antiallergic activity of tazifylline in the 10-15 mg dose range was superior to 5 mg without the intervention of clinically significant sedative effects at any of the 3 dose levels tested.

Intravenous nicardipine in patients with chronic heart failure: a nuclear stethoscope study.

The effects of intravenous nicardipine (10 mg) on some aspects of left ventricular function have been studied with a radioisotope method in 10 male patients in chronic heart failure (NYHA Class II and III). Blood pressure (mean +/- s.d.) fell from 133 +/- 26/86 +/- 11 mm Hg to 103 +/- 22/69 +/- 13. Heart rate rose from 67 +/- 9 beats per minute to 85 +/- 10. Left ventricular ejection fraction rose from 31 +/- 7% to 38 +/- 6% and relative cardiac output from 24 +/- 9 to 41 +/- 11 (P less than 0.001 in all cases). This suggests that nicardipine has a potent vasodilator effect which results in increased left ventricular pumping activity in patients with mild to moderate heart failure.